The GDF11 Promotes Nerve Regeneration After Sciatic Nerve Injury in Adult Rats by Promoting Axon Growth and Inhibiting Neuronal Apoptosis
Introduction: Sciatic nerve injury is a common injury of the nervous system. Stem cell-based therapies, drug-based therapies and rehabilitation physiotherapy therapies are currently available, but their limited therapeutic efficacy limits their use. Here, we aimed to explore a novel lentiviral-based...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-01-01
|
| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2021.803052/full |
| _version_ | 1819282814024024064 |
|---|---|
| author | Junhao Lin Jie Shi Jie Shi Jie Shi Xiang Min Si Chen Yunpeng Zhao Yuanqiang Zhang Lei Cheng |
| author_facet | Junhao Lin Jie Shi Jie Shi Jie Shi Xiang Min Si Chen Yunpeng Zhao Yuanqiang Zhang Lei Cheng |
| author_sort | Junhao Lin |
| collection | DOAJ |
| description | Introduction: Sciatic nerve injury is a common injury of the nervous system. Stem cell-based therapies, drug-based therapies and rehabilitation physiotherapy therapies are currently available, but their limited therapeutic efficacy limits their use. Here, we aimed to explore a novel lentiviral-based gene therapeutic strategy and to elaborate its mechanism.Materials and Methods: Recombinant GDF11 protein was used for the in vitro treatment of dorsal root ganglion (DRG) cells. Lentivirus was used to construct a vector system for the in vivo expression of GDF11. The nerve conduction function was detected using action-evoked potentials at different time periods, and the regulatory effect of nerves on target organs was detected by weighing the gastrocnemius muscle. Immunofluorescence of NF200 and S100 was used to show the regeneration of the sciatic nerve, and myelin and Nissl staining were performed to observe the pathological features of the tissue. Western was used to validate signaling pathways. The expression of related genes was observed by qPCR and Western blotting, and cell apoptosis was detected by flow cytometry.Result: GDF11 promotes the axonal growth of DRG cells and inhibits DGR cell apoptosis in vitro. GDF11 acts by activating the Smad pathway. GDF11 promotes the recovery of damaged sciatic nerve function in rats, the regeneration of damaged sciatic nerves in rats, and myelin regeneration of damaged sciatic nerves in rats. GDF11 also exerts a protective effect on neuronal cells in rats.Conclusion: Based on the present study, we conclude that GDF11 promotes axonal growth and inhibits DRG cell apoptosis in vitro through the Smad pathway, and lentivirus-mediated GDF11 overexpression in vivo can promote the recovery of sciatic nerves after transection by promoting axonal growth and inhibiting neuronal apoptosis in the spinal cord. |
| first_indexed | 2024-12-24T01:21:33Z |
| format | Article |
| id | doaj.art-36426c2a731f4a4ab28f093fee223675 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-24T01:21:33Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-36426c2a731f4a4ab28f093fee2236752022-12-21T17:22:38ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852022-01-01910.3389/fbioe.2021.803052803052The GDF11 Promotes Nerve Regeneration After Sciatic Nerve Injury in Adult Rats by Promoting Axon Growth and Inhibiting Neuronal ApoptosisJunhao Lin0Jie Shi1Jie Shi2Jie Shi3Xiang Min4Si Chen5Yunpeng Zhao6Yuanqiang Zhang7Lei Cheng8Department of Orthopaedic, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Orthopaedic, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaCheeloo College of Medicine, Shandong University, Jinan, ChinaNHC Key Laboratory of Otorhinolaryngology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Health Management Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Neurosurgery, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of Orthopaedic, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Orthopaedic, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaDepartment of Orthopaedic, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaIntroduction: Sciatic nerve injury is a common injury of the nervous system. Stem cell-based therapies, drug-based therapies and rehabilitation physiotherapy therapies are currently available, but their limited therapeutic efficacy limits their use. Here, we aimed to explore a novel lentiviral-based gene therapeutic strategy and to elaborate its mechanism.Materials and Methods: Recombinant GDF11 protein was used for the in vitro treatment of dorsal root ganglion (DRG) cells. Lentivirus was used to construct a vector system for the in vivo expression of GDF11. The nerve conduction function was detected using action-evoked potentials at different time periods, and the regulatory effect of nerves on target organs was detected by weighing the gastrocnemius muscle. Immunofluorescence of NF200 and S100 was used to show the regeneration of the sciatic nerve, and myelin and Nissl staining were performed to observe the pathological features of the tissue. Western was used to validate signaling pathways. The expression of related genes was observed by qPCR and Western blotting, and cell apoptosis was detected by flow cytometry.Result: GDF11 promotes the axonal growth of DRG cells and inhibits DGR cell apoptosis in vitro. GDF11 acts by activating the Smad pathway. GDF11 promotes the recovery of damaged sciatic nerve function in rats, the regeneration of damaged sciatic nerves in rats, and myelin regeneration of damaged sciatic nerves in rats. GDF11 also exerts a protective effect on neuronal cells in rats.Conclusion: Based on the present study, we conclude that GDF11 promotes axonal growth and inhibits DRG cell apoptosis in vitro through the Smad pathway, and lentivirus-mediated GDF11 overexpression in vivo can promote the recovery of sciatic nerves after transection by promoting axonal growth and inhibiting neuronal apoptosis in the spinal cord.https://www.frontiersin.org/articles/10.3389/fbioe.2021.803052/fullsciatic nerve injurynerve regenerationlentiviral vectorgrowth differentiation factor 11smad pathway |
| spellingShingle | Junhao Lin Jie Shi Jie Shi Jie Shi Xiang Min Si Chen Yunpeng Zhao Yuanqiang Zhang Lei Cheng The GDF11 Promotes Nerve Regeneration After Sciatic Nerve Injury in Adult Rats by Promoting Axon Growth and Inhibiting Neuronal Apoptosis Frontiers in Bioengineering and Biotechnology sciatic nerve injury nerve regeneration lentiviral vector growth differentiation factor 11 smad pathway |
| title | The GDF11 Promotes Nerve Regeneration After Sciatic Nerve Injury in Adult Rats by Promoting Axon Growth and Inhibiting Neuronal Apoptosis |
| title_full | The GDF11 Promotes Nerve Regeneration After Sciatic Nerve Injury in Adult Rats by Promoting Axon Growth and Inhibiting Neuronal Apoptosis |
| title_fullStr | The GDF11 Promotes Nerve Regeneration After Sciatic Nerve Injury in Adult Rats by Promoting Axon Growth and Inhibiting Neuronal Apoptosis |
| title_full_unstemmed | The GDF11 Promotes Nerve Regeneration After Sciatic Nerve Injury in Adult Rats by Promoting Axon Growth and Inhibiting Neuronal Apoptosis |
| title_short | The GDF11 Promotes Nerve Regeneration After Sciatic Nerve Injury in Adult Rats by Promoting Axon Growth and Inhibiting Neuronal Apoptosis |
| title_sort | gdf11 promotes nerve regeneration after sciatic nerve injury in adult rats by promoting axon growth and inhibiting neuronal apoptosis |
| topic | sciatic nerve injury nerve regeneration lentiviral vector growth differentiation factor 11 smad pathway |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2021.803052/full |
| work_keys_str_mv | AT junhaolin thegdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT jieshi thegdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT jieshi thegdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT jieshi thegdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT xiangmin thegdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT sichen thegdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT yunpengzhao thegdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT yuanqiangzhang thegdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT leicheng thegdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT junhaolin gdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT jieshi gdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT jieshi gdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT jieshi gdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT xiangmin gdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT sichen gdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT yunpengzhao gdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT yuanqiangzhang gdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis AT leicheng gdf11promotesnerveregenerationaftersciaticnerveinjuryinadultratsbypromotingaxongrowthandinhibitingneuronalapoptosis |